Liposomes containing lipid A: a potent nontoxic adjuvant for a human malaria sporozoite vaccine.
Liposomes containing lipid A have been developed as adjuvants for inducing humoral immunity to synthetic antigens containing repeat sequence epitopes from the circumsporozoite protein of Plasmodium falciparum. Preclinical studies demonstrated that liposomes containing lipid A and encapsulated antigen could overcome immunosuppression observed with antigen alone. When liposomes containing lipid A were adsorbed with aluminum hydroxide (alum), further stimulation of humoral immunity against encapsulated antigen was observed in animals. In the presence of huge doses of liposomal lipid A pyrogenicity was not observed and adjuvant activity was enhanced. A phase I human clinical trial has been initiated utilizing a vaccine containing a synthetic recombinant antigen and monophosphoryl lipid A in liposomes and nonliposomal alum as a further adjuvant. Preliminary results confirm that the vaccine lacks significant acute toxicity in humans and causes very strong specific humoral immunity against the appropriate epitopes of the target antigen.
Alving
C R
CR
Department of Membrane Biochemistry, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
Richards
R L
RL
D000276:Adjuvants, Immunologic; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D006801:Humans; D008050:Lipid A / Q000276:immunology*; D008081:Liposomes / Q000276:immunology* / Q000493:pharmacokinetics; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins; D016052:Protozoan Vaccines / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology
D000276:Adjuvants, Immunologic; D000953:Antigens, Protozoan; D008050:Lipid A; D008081:Liposomes; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D014614:Vaccines, Synthetic; C041595:circumsporozoite protein, Protozoan